EFFICACY OF PYRIDOXAL TREATMENT IN CONTROLLING THE GROWTH OF MELANOMAS IN CELL-CULTURE AND AN ANIMAL PILOT-STUDY

We have demonstrated, using confocal laser scanning microscopy, that p yridoxal treatment of B16C3 murine melanoma cells inhibits triamcinolo ne acetonide induced translocation of the glucocorticoid receptor to t he nucleus of intact cells. In addition to inhibiting glucocorticoid r eceptor nuclear translocation, pyridoxal kills B16C3 murine melanoma c ells and WM983A human melanoma cells in culture. Cortexolone, a glucoc orticoid antagonist, also kills cells in culture. This mechanism, howe ver, appears to initiate in the glucocorticoid receptor signal transdu cing cascade at a point prior to the impact of pyridoxal treatment alo ne. The glucocorticoid antagonist RU486 has no detrimental effect on m elanoma cell viability, however, in combination with pyridoxal, RU486 extends cell viability. Since pyridoxal kills melanoma cells in cultur e, a pilot study was carried out examining the efficacy of topical app lication of a pyridoxal cream to inhibit the growth and/or cause regre ssion of (B16C3) xenograft melanoma tumors in an immunocompetent (Hair less Rhino-J(3)) and an immunocompromised (Crl: nu/nu (CD1 (R))BR) mur ine animal model. The results of the study with immunocompetent animal s are encouraging. While tumors are brought under control by pyridoxal treatment, further work is needed to determine the most efficacious t reatment regimen and to establish formal concentrations for pyridoxal in topical ointments. Trials using immunocompromised animals indicated that although some qualitative differences may be detected between th e control and experimental animals, tumor growth in these animals is s o aggressive that multiple applications or higher concentrations of py ridoxal may be needed to obtain useful data.